1. Field
This application relates to compositions comprising carbon nanotubes and anti-tumor drugs and to method of using these compositions.
2. Background of the Technology
In addition to precise targeting tumor and toxicity concerns, drug resistance remains a major obstacle for the treatment of advanced cancerous tumors. Etoposide is one of the most widely used chemotherapeutic drugs. Etoposide is a derivative of podophyllotoxin with apoptotic action due to its ability to inhibit the topoisomerase II enzyme.
Etoposide is commonly used in the treatment of different malignant neoplasms such as Ewing's sarcoma, leukemia, and tumors of the brain, lung, testis, stomach and pancreas. Despite advances in treatment protocols, etoposide still has a modest response rate which varies from 1-5% in pancreatic cancer, 4% in breast cancer, 6% in ovarian cancer, 8% in cervical cancer, 19% in gastric cancer, and up to 45% in small cell lung cancer. There is an active worldwide ongoing research aiming to block the resistance response of malign cells to etoposide and other chemotherapeutic agents.
During the past decade there has been a rapid growth of research in the areas of nanomaterials and nanoscience because of the realization that these small size materials can be used in a multitude of industrial and biomedical processes. Some of the most promising applications include structural engineering, electronics, optics, consumer products, alternative energy, soil and water remediation, or for medicinal uses as therapeutic, diagnostic or drug delivery devices [49]. The promising field of nanomedicine offers the potential of monitoring, repairing, constructing and controlling human biological systems at the molecular level [49, 36] and has resulted in the engagement by drug companies in a wide array of nanotechnology research. Despite these potential benefits to society, there is concern that exposure of humans to certain types of nanomaterials may lead to significant adverse health outcomes. Among these nanomaterials, specific concern is expressed about the possible toxicity of nanoparticles (NP), which may be defined as materials with a diameter below 100 nm, and nanotubes (NT) which have two dimensions below 100 nm but the third (axial) dimension can be much larger [36]. The scientific community is responding to these concerns by consideration of the challenges to understanding exposure pathways and toxicokinetics and applying current toxicology testing methodologies, including in vitro and in vivo systems, previously used to understand the toxicology of air pollutant particles, metal fumes, radionuclides, nuisance dust, silica, asbestos and synthetic fibers [49]. However, it is also recognized that, because of the development of new methodologies derived from emerging technologies like DNA microarray, proteomics and metabolomics, new thinking is required not only in understanding toxicology associated with nanomaterials, but in the understanding of all toxicants to which the human is exposed [47]. Because of the unique dimensional and morphological properties of nanomaterials, a large number of applications have been developed that hold significant promise in the successful targeting of cancer [43, 58], tumor ablation [57, 42], drug and gene delivery [50] and especially tissue engineering [41]. Additionally, a large number of research publications have indicated that nanomaterials have the ability to interact very strongly with a variety of biological systems. For example, it was shown that titanium dioxide (TiO2) nano-morphologically modified coatings can be used to reduce the adverse inflammatory effects of titanium implants and promote more advanced tissue healing following surgical procedures [39]. Also, a number of cell lines of different origins have been shown to grow on nanobased substrates, such as carbon nanotubes or other nanomaterials, indicating their potential use to evaluate the efficacy of nano-products as well as potential toxicity of nanomaterials [56]. Moreover its been amply demonstrated that there is a reasonably rapid uptake of nanomaterials into cells resulting in the interaction of these nanomaterials with various subcellular components and organelles indicating their potential for delivery to different cellular compartments [44, 55]. Therefore, a more thorough understanding of the potential cytotoxic effects of such nanomaterials is required.
Accordingly, there still exists a need for improved compositions and methods for treating cancer.